Ever wished you could hit the pause button on ageing? At least one creature may do just that. Axolotls seem to halt one of the hallmarks of the process part way through their lives, a finding that could shed new light on ageing and regeneration.
Axolotls (Ambystoma mexicanum) belong to a group of amphibians called salamanders, which are famed for their astonishing powers of regeneration, such as regrowing amputated limbs. They also appear to age very little, a feature called negligible senescence.
But scientists know little about how axolotls achieve negligible senescence, if they truly do. Even their cause of death is a mystery. 鈥淏asically, no one in the field knows what axolotls die of,鈥� says at the Dresden University of Technology in Germany.
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To find out more, Yun and at Altos Labs in Cambridge, UK, and their colleagues studied one key hallmark of ageing called DNA methylation. This is one of several factors influencing epigenetics, or how genes are switched on or off, and it involves chemical markers on DNA.
In mammals and frogs, the pattern of marks across the genome changes over time. 快猫短视频s have created statistical models, called epigenetic clocks, that correlate these changing patterns with chronological age.
But the team could only build an epigenetic clock for the first four years of the axolotl鈥檚 lives, about a third of their average lifespan. 鈥淚t鈥檚 a weird phenomenon that I have not seen in any other species,鈥� says Horvath. Thereafter, the clock stopped: the animals鈥� methylation patterns remained stable. 鈥淭his is remarkable as it suggests that, at least at epigenetic levels, axolotls may indeed exhibit negligible senescence,鈥� says Yun.
Exactly how epigenetic changes contribute to ageing isn鈥檛 clear, but they seem to be linked to development and the way in which cells acquire their specialised functions during development. Artificially undoing cell specialisation, a process called reprogramming, 鈥渞ejuvenates鈥� cells, resetting their epigenetic clocks and wiping their memory.
When axolotls regenerate an amputated limb, their cells also undo cell specialisation, but only part way. 鈥淭hey retain a very strong identity of what they were, where they are and they know what parts of the limb are missing,鈥� says Yun.
When the team looked at the methylation patterns in regenerated axolotl limbs, they found that they were epigenetically younger than the rest of the animal. 鈥淚t鈥檚 an example of natural rejuvenation,鈥� says Yun.
All this raises the possibility that animals that can regenerate throughout life retain some kind of developmental flexibility that counteracts at least some ageing processes, says Yun, and their regenerative capacities may act together with evolutionary innovations that enable negligible senescence. 鈥淲e need to dig deeper into axolotl biology to be certain,鈥� says Yun.
鈥淚 think it鈥檚 fascinating,鈥� says at the University of Birmingham, UK. The findings fit with one theory that suggests ageing isn鈥檛 just wear and tear, but also the result of the developmental processes that build and maintain bodies not switching off when they are no longer needed. The axolotl study 鈥渟hows that there is a progression through biological time in these animals that stops after maturity,鈥� he says.
But some questions remain. For de Magalh茫es, the main one is whether axolotls are truly an example of a non-ageing species. 鈥淲e lack detailed studies,鈥� he says. It would be important to determine whether these epigenetic patterns are in line with studies of the axolotl鈥檚 physical properties and abilities across its life course, he says.
bioRxiv
